The Histology, Biochemistry, and Molecular Imaging (HBMI) Core will provide musculoskeletal histopathology, histomorphometry, biochemistry, cellular, and molecular imaging and analysis services to support the collaborative clinical and basic science components of the Center for Musculoskeletal Research (CMSR) all under a single administrative structure. The expansion and integration of services within the HBMI Core will further increase productivity, enhance the efficiency of the Core, and enable the translation between histological and histomorophometric data and the underlying biochemical, cellular, and molecular mechanisms. Additionally, the HBMI Core will develop novel technologies and approaches to generate and analyze histology, histomorphometry, biochemistry, cellular, and molecular data in the musculoskeletal sciences, which will accelerated the pace of research for all funded projects within the CMSR. The overall Specific Aims of the Core are to continue to: (1) Provide efficient and high quality histology, histomorphometry, biochemistry, cellular, and molecular imaging and analysis services within the musculoskeletal sciences; (2) Provide access to Research Assistant Professors (RAP) and Unfunded Physician Scientists (UPS), who will also assist the Core by providing unique and highly skilled mentoring within the musculoskeletal sciences through the utilization of cutting edge histological, biochemical, and molecular technologies; and (3) Innovate HBMI musculoskeletal basic and clinical research by developing novel technologies and integrated approaches. The primary goals related to Specific Aim 2 and 3 are to develop: 1) digital whole slide imaging (Olympus' NanoZoomer) technology to capture images for automated quantitative analysis of standard and novel parameters of bone and cartilage histomorphometry using VisioPharm's image analysis software and validate these parameters using the standardized OsteoMetrics histomorphometry system; 2) quantitative methodology using the NanoZoomer and VisioPharm image analysis software or the OsteoMetrics histomorphometry system to analyze protein and gene expression by immunohistochemistry (IHC) or in situ hybridization (ISH) in tissue samples of fracture callus, bone and cartilage; 3) Tissue Microarrays (TMAs) of murine and human tissues to optimize IHC analysis of protein expression and quantify expression automatically using the NanoZoomer system; and 4) novel high throughput cell based assays using the BioTek Synergy Mx multi-mode microplate reader to screen for important signaling pathway interactions that regulate musculoskeletal cell proliferation differentiation, and apoptosis. The translation between histological and histomorophometric data and the underlying biochemical, cellular, and molecular mechanisms will be facilitated by the HBMI Co-Directors (Dr, Matthew J. Hilton; PI and Dr. Brendan Boyce; Co-PI), which will oversee all of the components of the Core and assist in the development of new technologies to support funded research in the CMSR.